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Structure of the Oncoprotein Gankyrin in Complex with S6 ATPase of the 26S Proteasome
Structural highlights
FunctionPSD10_MOUSE Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module (By similarity). Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pahway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis. Acts as an oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedGankyrin is an oncoprotein commonly overexpressed in most hepatocellular carcinomas. Gankyrin interacts with S6 ATPase of the 19S regulatory particle of the 26S proteasome and enhances the degradation of the tumor suppressors pRb and p53. Here, we report the structure of gankyrin in complex with the C-terminal domain of S6 ATPase. Almost all of the seven ankyrin repeats of gankyrin interact, through its concave region, with the C-terminal domain of S6 ATPase. The intermolecular interactions occur through the complementary charged residues between gankyrin and S6 ATPase. Biochemical studies based on the structure of the complex revealed that gankyrin interacts with pRb in both the presence and absence of S6 ATPase; however, the E182 residue in gankyrin is essential for the pRb interaction. These results provide a structural basis for the involvement of gankyrin in the pRb degradation pathway, through its association with S6 ATPase of the 26S proteasome. Structure of the oncoprotein gankyrin in complex with S6 ATPase of the 26S proteasome.,Nakamura Y, Nakano K, Umehara T, Kimura M, Hayashizaki Y, Tanaka A, Horikoshi M, Padmanabhan B, Yokoyama S Structure. 2007 Feb;15(2):179-89. PMID:17292836[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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